Cardiac-restricted IGF-1Ea overexpression reduces the early accumulation of inflammatory myeloid cells and mediates expression of extracellular matrix remodelling genes after myocardial infarction

Strategies to limit damage and improve repair after myocardial infarct remain a major therapeutic goal in cardiology. Our previous studies have shown that constitutive expression of a locally acting insulin-like growth factor-1 Ea (IGF-1Ea) propeptide promotes functional restoration after cardiac injury associated with decreased scar formation. In the current study, we investigated the underlying molecular and cellular mechanisms behind the enhanced functional recovery. We observed improved cardiac function in mice overexpressing cardiac-specific IGF-1Ea as early as day 7 after myocardial infarction. Analysis of gene transcription revealed that supplemental IGF-1Ea regulated expression of key metalloproteinases (MMP-2 and MMP-9), their inhibitors (TIMP-1 and TIMP-2), and collagen types (Col 1α1 and Col 1α3) in the first week after injury. Infiltration of inflammatory cells, which direct the remodelling process, was also altered; in particular there was a notable reduction in inflammatory Ly6C+ monocytes at day 3 and an increase in anti-inflammatory CD206+ macrophages at day 7. Taken together, these results indicate that the IGF-1Ea transgene shifts the balance of innate immune cell populations early after infarction, favouring a reduction in inflammatory myeloid cells. This correlates with reduced extracellular matrix remodelling and changes in collagen composition that may confer enhanced scar elasticity and improved cardiac function

Superconducting properties of the attractive Hubbard model

A self-consistent set of equations for the one-electron self-energy in the ladder approximation is derived for the attractive Hubbard model in the superconducting state. The equations provide an extension of a T-matrix formalism recently used to study the effect of electron correlations on normal-state properties. An approximation to the set of equations is solved numerically in the intermediate coupling regime, and the one-particle spectral functions are found to have four peaks. This feature is traced back to a peak in the self-energy, which is related to the formation of real-space bound states. For comparison we extend the moment approach to the superconducting state and discuss the crossover from the weak (BCS) to the intermediate coupling regime from the perspective of single-particle spectral densities.Comment: RevTeX format, 8 figures. Accepted for publication in Z.Phys.

Methane storms as a driver of Titan's dune orientation

Titan's equatorial regions are covered by eastward propagating linear dunes. This direction is opposite to mean surface winds simulated by Global Climate Models (GCMs), which are oriented westward at these latitudes, similar to trade winds on Earth. Different hypotheses have been proposed to address this apparent contradiction, involving Saturn's gravitational tides, large scale topography or wind statistics, but none of them can explain a global eastward dune propagation in the equatorial band. Here we analyse the impact of equinoctial tropical methane storms developing in the superrotating atmosphere (i.e. the eastward winds at high altitude) on Titan's dune orientation. Using mesoscale simulations of convective methane clouds with a GCM wind profile featuring superrotation, we show that Titan's storms should produce fast eastward gust fronts above the surface. Such gusts dominate the aeolian transport, allowing dunes to extend eastward. This analysis therefore suggests a coupling between superrotation, tropical methane storms and dune formation on Titan. Furthermore, together with GCM predictions and analogies to some terrestrial dune fields, this work provides a general framework explaining several major features of Titan's dunes: linear shape, eastward propagation and poleward divergence, and implies an equatorial origin of Titan's dune sand.Comment: Published online on Nature Geoscience on 13 April 201

A model of top-down gain control in the auditory system

To evaluate a model of top-down gain control in the auditory system, 6 participants were asked to identify 1-kHz pure tones differing only in intensity. There were three 20-session conditions: (1) four soft tones (25, 30, 35, and 40 dB SPL) in the set; (2) those four soft tones plus a 50-dB SPL tone; and (3) the four soft tones plus an 80-dB SPL tone. The results were well described by a top-down, nonlinear gain-control system in which the amplifier’s gain depended on the highest intensity in the stimulus set. Individual participants’ identification judgments were generally compatible with an equal-variance signal-detection model in which the mean locations of the distribution of effects along the decision axis were determined by the operation of this nonlinear amplification system

Discovery of a jet from the single HAe/Be star HD 100546

Young accreting stars drive outflows that collimate into jets, which can be seen hundreds of au from their driving sources. Accretion and outflow activity cease with system age, and it is believed that magneto-centrifugally launched disk winds are critical agents in regulating accretion through the protoplanetary disk. Protostellar jets are well studied in classical T Tauri stars (M⋆ ≲ 2 M⊙), while few nearby (d ≲ 150 pc) intermediate-mass stars (M⋆ = 2−10 M⊙), known as Herbig Ae/Be stars, have detected jets. We report VLT/MUSE observations of the Herbig Ae/Be star HD 100546 and the discovery of a protostellar jet. The jet is similar in appearance to jets driven by low-mass stars and compares well with the jet of HD 163296, the only other known optical jet from a nearby Herbig Ae/Be star. We derive a (one-sided) mass-loss rate in the jet of log Ṁjet ∼ −9.5 (in M⊙ yr−1) and a ratio of outflow to accretion of roughly 3 × 10−3, which is lower than that of CTTS jets. The discovery of the HD 100546 jet is particularly interesting because the protoplanetary disk around HD 100546 shows a large radial gap, spiral structure, and might host a protoplanetary system. A bar-like structure previously seen in Hα with VLT/SPHERE shares the jet position angle, likely represents the base of the jet, and suggests a jet-launching region within about 2 au. We conclude that the evolution of the disk at radii beyond a few au does not affect the ability of the system to launch jets

Chronic Intermittent Materno-Fetal Hyperoxygenation in Late Gestation May Improve on Hypoplastic Cardiovascular Structures Associated with Cardiac Malformations in Human Fetuses

Hypoplasia of cardiovascular structures is a common finding in fetuses with cardiac malformations. Materno-fetal hyperoxygenation (HO) during late gestation promotes venous return to the fetal heart. This analysis in human fetuses sought to define whether this “loading” effect might improve hypoplastic cardiovascular dimensions. Fifteen late-gestation fetuses presented with varying degrees of hypoplastic cardiovascular structures. In these cases, chronic intermittent materno-fetal HO was administered during periods ranging from 8 to 33 days. Cardiac measurements were taken before and at the end of treatment and translated into Z-scores as well as plotted on normal growth charts. During the treatment period, chronic intermittent materno-fetal HO was associated with improved dimensions of ≥1 hypoplastic cardiovascular structures in most fetuses. However, in some cases, the effect of HO was neutralized or impaired by the presence of ventricular septal defects as well as obstructions to ventricular filling or emptying. Chronic intermittent materno-fetal HO near term may be associated with improvements of hypoplastic cardiovascular dimensions in fetuses with a spectrum of cardiac malformations. This effect may facilitate postnatal treatment and improve prognosis in suitable cases

Hypofractionated image-guided breath-hold SABR (Stereotactic Ablative Body Radiotherapy) of liver metastases - clinical results

Purpose: Stereotactic Ablative Body Radiotherapy (SABR) is a non-invasive therapy option for inoperable liver oligometastases. Outcome and toxicity were retrospectively evaluated in a single-institution patient cohort who had undergone ultrasound-guided breath-hold SABR. Patients and methods: 19 patients with liver metastases of various primary tumors consecutively treated with SABR (image-guidance with stereotactic ultrasound in combination with computer-controlled breath-hold) were analysed regarding overall-survival (OS), progression-free-survival (PFS), progression pattern, local control (LC), acute and late toxicity. Results: PTV (planning target volume)-size was 108 +/- 109cm(3) (median 67.4 cm(3)). BED2 (Biologically effective dose in 2 Gy fraction) was 83.3 +/- 26.2 Gy (median 78 Gy). Median follow-up and median OS were 12 months. Actuarial 2-year-OS-rate was 31%. Median PFS was 4 months, actuarial 1-year-PFS-rate was 20%. Site of first progression was predominantly distant. Regression of irradiated lesions was observed in 84% (median time to detection of regression was 2 months). Actuarial 6-month-LC-rate was 92%, 1- and 2-years-LC-rate 57%, respectively. BED2 influenced LC. When a cut-off of BED2 = 78 Gy was used, the higher BED2 values resulted in improved local control with a statistical trend to significance (p = 0.0999). Larger PTV-sizes, inversely correlated with applied dose, resulted in lower local control, also with a trend to significance (p-value = 0.08) when a volume cut-off of 67 cm(3) was used. No local relapse was observed at PTV-sizes < 67 cm(3) and BED2 > 78 Gy. No acute clinical toxicity > degrees 2 was observed. Late toxicity was also <= degrees 2 with the exception of one gastrointestinal bleeding-episode 1 year post-SABR. A statistically significant elevation in the acute phase was observed for alkaline-phosphatase; in the chronic phase for alkaline-phosphatase, bilirubine, cholinesterase and C-reactive protein. Conclusions: A trend to statistically significant correlation of local progression was observed for BED2 and PTV-size. Dose-levels BED2 > 78 Gy cannot be reached in large lesions constituting a significant fraction of this series. Image-guided SABR (igSABR) is therefore an effective non-invasive treatment modality with low toxicity in patients with small inoperable liver metastases

The pre-main sequence binary HK Ori : Spectro-astrometry and EXPORT data

In this paper we present multi-epoch observations of the pre-main sequence binary HK Ori. These data have been drawn from the EXPORT database and are complemented by high quality spectro-astrometric data of the system. The spectroscopic data appear to be very well represented by a combination of an A dwarf star spectrum superposed on a (sub-)giant G-type spectrum. The radial velocity of the system is consistent with previous determinations, and does not reveal binary motion, as expected for a wide binary. The spectral, photometric and polarimetric properties and variability of the system indicate that the active object in the system is a T Tauri star with UX Ori characteristics. The spectro-astrometry of HK Ori is sensitive down to milli-arcsecond scales and confirms the speckle interferometric results from Leinert et al. The spectro-astrometry allows with fair certainty the identification of the active star within the binary, which we suggest to be a G-type T Tauri star based on its spectral characteristics.Comment: MNRAS in press 8 pages 7 figure

Probing the Universe with Weak Lensing

Gravitational lenses can provide crucial information on the geometry of the Universe, on the cosmological scenario of formation of its structures as well as on the history of its components with look-back time. In this review, I focus on the most recent results obtained during the last five years from the analysis of the weak lensing regime. The interest of weak lensing as a probe of dark matter and the for study of the coupling between light and mass on scales of clusters of galaxies, large scale structures and galaxies is discussed first. Then I present the impact of weak lensing for the study of distant galaxies and of the population of lensed sources as function of redshift. Finally, I discuss the potential interest of weak lensing to constrain the cosmological parameters, either from pure geometrical effects observed in peculiar lenses, or from the coupling of weak lensing with the CMB.Comment: To appear Annual Review of Astronomy and Astrophysiscs Vol. 37. Latex and psfig.sty. Version without figure, 54 pages, 73Kb. Complete version including 13 figures (60 pages) available on ftp.iap.fr anonymous account in /pub/from_users/mellier/AnnualReview ; file ARAAmellier.ps.gz 1.6 M

Synaptic transmission parallels neuromodulation in a central food-intake circuit

NeuromedinU is a potent regulator of food intake and activity in mammals. In Drosophila, neurons producing the homologous neuropeptide hugin regulate feeding and locomotion in a similar manner. Here, we use EM-based reconstruction to generate the entire connectome of hugin-producing neurons in the Drosophila larval CNS. We demonstrate that hugin neurons use synaptic transmission in addition to peptidergic neuromodulation and identify acetylcholine as a key transmitter. Hugin neuropeptide and acetylcholine are both necessary for the regulatory effect on feeding. We further show that subtypes of hugin neurons connect chemosensory to endocrine system by combinations of synaptic and peptide-receptor connections. Targets include endocrine neurons producing DH44, a CRH-like peptide, and insulin-like peptides. Homologs of these peptides are likewise downstream of neuromedinU, revealing striking parallels in flies and mammals. We propose that hugin neurons are part of an ancient physiological control system that has been conserved at functional and molecular level.SFB 645 and 704, DFG Cluster of Excellence ImmunoSensation, DFG grant PA 787, HHMI Janeli